Ferreting for Facts in the Realm of Clinical Trials

By JANE E. BRODY

illions of women discovered a basic in medicine, much to their dismay, this summer when the Women's Health Initiative study showed that postmenopausal hormone replacement did not prevent heart attacks. Only clinical trials, they learned, can establish a definitive fact about the effectiveness and safety of a diagnostic technique, preventive method or treatment.

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Experience with patients in doctors' offices and hospitals and observational studies like the Nurses' Health Study can offer hints, sometimes strong ones, on benefits and risks of various procedures and habits, but they are still only guesstimates.

Turning a hint into a hard-to-refute fact requires a clinical trial in which participants are randomly assigned to one procedural group or another. Even then, the findings can be applied with certainty only to the kinds of people or circumstances used in the trial.

Lifesaving Progress
 

Clinical trials are the backbones of medical progress. They have demonstrated the value of vaccines to prevent devastating diseases and drugs to treat them. They have shown, for example, that certain drugs given immediately after a heart attack or stroke can markedly increase survival while others do not help. And clinical trials are behind nearly all the progress that has been made in treating various kinds of cancers in the last four decades.

Treatments that now save the lives of most children with acute leukemia and most young adults with Hodgkin's disease were established through clinical trials. So was the replacement of radical mastectomies, the standard therapy for breast cancer for more than half a century, with lesser procedures like simple mastectomies and, more common now, lumpectomies followed by radiation therapy and sometimes chemotherapy.

The newer therapies are not only less damaging to a woman's body and self-image but are also associated with better survival rates. Thanks largely to the findings of clinical trials, the five-year survival rate for all stages of breast cancer is nearing 84 percent, and rates for melanoma and cancers of the cervix, uterus, prostate and bladder exceed 90 percent.

Yet, only 3 percent to 5 percent of cancer patients take part in clinical trials, which test standard therapies against new approaches that may or may not be better than the standard. It usually takes three years to enroll enough patients in a cancer trial to produce statistically significant results, a simple fact that delays progress in the fight against cancer.

Why More Don't Participate
 

Misconceptions about the nature of clinical trials, along with insurance hurdles, contribute to the reluctance of many cancer patients to join clinical trials and, often, their doctors' reluctance to suggest that they participate. Cancer Care, a national organization at (800) 813-4673 that offers free education and support for cancer patients and their families, attributes this reluctance mainly to a lack of information and fear of research.

Many people fear that participating means they will be guinea pigs who could receive dangerous treatments that would make things worse, not better. But before patients are enrolled in clinical trials, the treatments have undergone several preliminary tests. After laboratory tests and animal studies show promising results, new treatments go through two tests in patients.

The first, a Phase 1 study, involves a small number of patients (maybe a dozen or two) who cannot be helped by other known treatments. In this phase, researchers look for the best way to administer a new treatment, how it can be used safely and if there may be harmful side effects.

Next, a Phase 2 trial involves perhaps 100 patients, looking for a treatment benefit. In the case of a cancer drug, for example, does it shrink the tumor? Is it less damaging than existing therapies?

Finally, comes the big Phase 3 trial involving hundreds and perhaps thousands of patients around the country. In it, the new treatment is compared directly with standard therapy. At this point, patients are randomly assigned to groups taking the new therapy or the old one.

Patients may not be told which treatment they are receiving and sometimes the doctors who care for them do not know until the trial ends. This is to avoid bias, the unintentional exaggeration of the benefits or risks of the new therapy.

Before patients are enrolled in clinical trials, they must be told in detail, orally and in writing, what it will involve. Then, they are asked to sign informed consent forms that fully describe the studies and their potential risks and benefits.

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Patients are not obligated to complete the study, and they can drop out at any time for any reason. If too many leave, however, the study findings may have no validity.

In the course of a study, the safety and effectiveness of the treatment being tested are independently monitored. If at any point it appears to be less effective or more hazardous than the standard — or if the new therapy is far better than the standard — the trial will be discontinued.

This is precisely what happened with the Women's Health Initiative study. Once the risks of hormone replacement were found to exceed a certain preset level of safety, the trial was prematurely ended.

Benefits and Risks
 

At the very least, by joining a clinical trial, you will receive the best established therapy. At most, you will be among the first to receive a treatment that proves to be better, either more effective or less hazardous. All participants in clinical trials also receive high-quality care and are likely to be closely monitored and tested to assess their progress.

For those with an altruistic bent, trial participants also have the opportunity to help others through improved treatments that then become widely used. This is exactly what happened as a result of the breast cancer treatment trials.

You do not necessarily have to live in the vicinity of a major cancer center to participate in a cancer treatment trial. More and more community hospitals are getting involved, and in some cases the financing covers transportation to a trial center.

To be sure, there can be drawbacks to trial participation. As the National Cancer Center points out in its excellent booklet, "Taking Part in Clinical Trials: What Cancer Patients Need to Know": "New treatments under study are not always better than, or even as good as, standard care. They may have side effects that doctors do not expect or that are worse than those of standard treatment."

Even if a new treatment proves to be better than the standard, it may not work for every patient.

Then there is the medical insurance issue. Some providers refuse to cover the costs of what they view as experimental treatment.

While study participants are not charged for the remedy being tested (which can costs hundreds of dollars for each treatment), they are usually responsible for all ancillary costs. It is best to check with your insurer to find out what will be covered before you decide to take part in a clinical trial.

Find out, too, just what participation will involve, including the kinds of tests that will be done and how often, where treatment will be administered and for how long, who will be in charge of your care, whether your own doctor will be involved and if there will be follow-up care or tests after the study has ended.